December 10, 2012

Accurate genetic test for TB a step to eliminating killer disease

Technology Review - GeneXpert resembles a high-end espresso maker. The device is simple to use. A technician squirts a sputum ­sample from a patient into what looks like a printer cartridge and then clicks that into the machine, which performs a reaction that amplifies specific bits of M. tuberculosis DNA if they are present. Fluorescent molecules light up when they come in contact with the targeted DNA, and the machine detects the fluorescence, sending the information to a computer. The entire process takes a mere two hours. Not only can GeneXpert detect the presence of the TB-causing bacteria, but it can accurately determine whether the bacterial DNA has the mutations known to make the disease resistant to the most commonly used drug.

In 2011, an estimated 8.7 million people became sick from M. tuberculosis. Roughly 1.4 million people die of TB each year; HIV is the only infectious agent that kills more.

One critical reason this epidemic continues is that there’s no effective and affordable way to tell who is infected. TB goes undiagnosed in some three million people each year. Some simply are never tested. Others, because of antiquated diagnostic technologies, are wrongly given a clean bill of health. Traditional diagnosis for TB relies on staining a sputum sample with dyes and then examining a slide under a microscope to look for the bacteria. This “smear” test, developed 125 years ago, detects fewer than 60 percent of all cases and doesn’t identify drug-­resistant strains. The more precise culture test to determine sensitivity to certain drugs takes longer, costs more, and needs to be done in a well-equipped lab—so it is used sparingly. That means roughly 80 percent of the drug-resistant cases in the world go undetected, according to the World Health Organization. Together, these undiagnosed individuals represent a vast reservoir for the bacteria, including drug-resistant strains. Infection flourishes and leapfrogs through communities, devastating the most vulnerable people, such as those already weakened by HIV.

A practical, quick, and powerful diagnostic tool could change that deadly dynamic. Brought to market by a public-private partnership between the University of Medicine and Dentistry of New Jersey, the Foundation for Innovative New Diagnostics in Geneva, Switzerland, and Cepheid, a manufacturer based in Sunnyvale, California, the GeneXpert TB detection machine gained approval from the WHO in December 2010. A few months later, South Africa’s health minister, Aaron Motsoaledi, compared the machines to “bazookas” in the war against TB and pledged to place them in each of the country’s 52 districts.

deploying ­GeneXpert requires a significant investment by South Africa’s government. A four-­cartridge machine with a desktop computer sells for $17,000, and cartridges go for $9.98. Analyses show that a GeneXpert test in South Africa, including staff time and machine maintenance, costs roughly $25 per ­sample, versus $3 for a sputum smear and $12 to $16 for a culture. The increased cost is offset to a degree by the fact that GeneXpert incorporates resistance testing—traditional drug sensitivity testing for first-line treatments costs $72 per test—but all told, a paper published by PLOS ONE found, South Africa will have to spend 55 percent more per suspected TB case if it fully scales up the use of the technology as planned.

The flip side is that the country will receive serious bang for its rand, because the costs of the machine are dwarfed by the expense of providing months of hospital care for TB patients. “The diagnosis costs are a very, very small fraction of the total TB control program, and there’s substantial benefit,” says Mark Nicol, a clinical microbiologist who has a joint appointment at the University of Cape Town and the government’s National Health Laboratory Service. Nicol notes that poorer countries with high TB burdens will need outside help. “But it’s a price that South Africa certainly can afford,” he says.

Eleven TB vaccines are currently in clinical trials, a reflection of the intense efforts over the past decade to rejuvenate the field, but none has yet warranted a full-scale efficacy study. The World Health Organization estimates that the earliest a vaccine could be licensed is 2020.